Zolpidem and triazolam interact differentially with a delay interval on a digit‐enter‐and‐recall task

Abstract

Zolpidem (AMBIEN((R))), an imidazopyridine, is now the most commonly prescribed hypnotic in the United States. Zolpidem is neuropharmacologically distinct from benzodiazepine hypnotics in that it binds with low affinity to alpha(5)-containing GABA(A)-receptor subtypes. Despite its unique benzodiazepine-receptor binding profile, the results of most of the published studies conducted with humans suggest that the absolute magnitude of impairment produced by zolpidem is comparable to that observed with benzodiazepine hypnotics like triazolam. The present study compared the acute effects of zolpidem (0, 7.5, 15 and 22.5 mg) and triazolam (0, 0.1875, 0.375 and 0.5625 mg) in 10 non-drug-abusing humans using a Digit-Enter-and-Recall task with varying delay intervals (0, 10 and 20 s). To more fully characterize the behavioral effects of zolpidem and triazolam, several other performance tasks and subject-rated drug-effect questionnaires were included. Zolpidem and triazolam impaired performance on the Digit-Enter-and-Recall task as a function of dose under all delay intervals. However, the dose-related effects of the drugs interacted differentially with the delay interval such that zolpidem produced significantly less impairment than triazolam following the longest delay (i.e., 20 s). Zolpidem and triazolam produced comparable dose-related impairment on the digit symbol substitution test (DSST), circular lights task, and picture recall/recognition task. Zolpidem and triazolam generally produced qualitatively and quantitatively similar subject-rated drug effects, although some between-drug differences were observed. Consistent with the pharmacokinetics of these drugs, the effects of zolpidem peaked sooner and were shorter in duration than those observed with triazolam. The results of this experiment suggest that zolpidem may have less potential than triazolam to impair recall, which may be due to differences between these compounds in terms of their benzodiazepine-receptor binding profile. The results of the present study are also concordant with previous studies that found that drugs that act at the GABA(A)-receptor complex can be differentiated based on their interaction with the delay interval on a Digit-Enter-and-Recall task. Copyright 2001 John Wiley & Sons, Ltd.

Discriminative‐Stimulus Effects of Triazolam in Light and Moderate Drinkers

“…These effects were qualitatively and quantitatively similar to those observed in previous studies conducted in our laboratory with this dose of triazolam (Rush and Ali, 1999;Rush and Baker, 2001;Rush et al, 1998).…”

“…The effects of triazolam during the test-of-novel-doses phase were an orderly function of dose. The effects of triazolam observed during the sampling, test-of-acquisition, and test-of-novel-doses phase were qualitatively and quantitatively similar to those reported previously with comparable doses (Rush and Ali, 1999;Rush and Baker, 2001;Rush et al, 1998).…”

“…The most commonly used clinical dose of triazolam is 0.25 mg (Physician's Desk Reference, 2000). In this experiment, we used a higher dose because previous research in our laboratory has shown that this dose produces robust behavioral effects (Rush and Ali, 1999;Rush and Baker, 2001;Rush et al, 1998). Perhaps significant differences between light and moderate drinkers in terms of the discriminative-stimulus effects of triazolam would emerge with a dose that produces more subtle effects.…”

A therapeutic dose of zolpidem has limited abuse-like effects in drug-naïve females: A pilot study

“…Similarly, the increase in a dysphoric-like item such as “nauseous” toward the end of the experimental session was not accompanied by a concomitant increase in lysergic acid diethylamide. However, the increase in ratings of “nauseous” as well as those of “dizzy”, “confused”, and feelings of “loose” agree with previous reports of zolpidem-induced nausea and/or emesis (Evans et al 1990; Rush and Griffiths, 1996; Rush et al 1999) as well as impaired concentration (Rush and Baker, 2001), although higher doses were used in those studies.…”

“…The present results in healthy participants agree with those previous studies (Rush and Griffiths, 1996; Rush et al, 1997; 1998) in that the pentobarbital-chlorpromazine-alcohol group was increased, although the other scales were unchanged. These data also support the notion that this dose of zolpidem may engender variable subjective effects (Rush and Baker, 2001) because the VAS did not necessarily change in parallel with the ARCI. For example, the increase in the pentobarbital-chlorpromazine-alcohol group was not accompanied by an increase in self-reported ratings of “sleepy”.…”